Recent advances in diagnosis of drug-induced liver injury

The most recent issue of Gut investigated the provision of more advanced scientific and regulatory guidance for safety assessment in drug-induced liver injury.

Idiosyncratic drug-induced liver injury is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug.

Although currently used liver parameters are sensitive in detecting drug-induced liver injury, they are neither specific nor able to predict the patient's subsequent clinical course.

Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with drug-induced liver injury.

Dr Gerd Kullak-Ublick and colleagues from Switzerland investigated the provision of more advanced scientific and regulatory guidance for liver safety assessment.

A novel drug-induced liver injury cluster score is being developed which predicts drug-induced liver injury

Gut

The team reported that new emerging biomarkers which could be useful in assessing drug-induced liver injury include total keratin18 and caspase-cleaved keratin18, macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122.

From the numerous in vitro test systems that are available, the researchers found that monocyte-derived hepatocytes generated from patients with drug-induced liver injury show promise in identifying the drug-induced liver injury-causing agent from among a panel of coprescribed drugs.

Several computer-based algorithms are available that rely on cumulative scores of known risk factors such as the administered dose or potential liabilities such as mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites.

The research team noted that a novel drug-induced liver injury cluster score is being developed which predicts drug-induced liver injury from multiple complimentary cluster and classification models using absorption–distribution–metabolism–elimination-related as well as physicochemical properties, diverse substructural descriptors and known structural liabilities.

Dr Kullak-Ublick's team comments, "The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing drug-induced liver injury registries, biobanks and public–private partnerships."